ROLE OF INHIBIN AND FRP PROTEINS IN ERYTHROPOIESIS

总体目标是调查最近两个 人类红细胞生成中的纯化蛋白。抑制素，一种 一种选择性地抑制分泌的促垂体激素 卵泡刺激素(FSH)，其特征是 一种由α-和β-多肽组成的异二聚体蛋白质。 FSH释放蛋白(FRP)是一种由以下组成的二聚体 两条抑制素β链。有人建议，它们可以构成 一种新的涉及两个人的红细胞生成的体液调控 具有相反功能的蛋白质二聚体。基于我们的 它们对红系分化的影响的最新发现， 建议进行以下分析，以深入了解他们的角色 在人类的红细胞生成中。 1.进一步研究FRP和抑制素对血管紧张素转换酶的影响 红系祖细胞：剂量反应、依赖关系 促红细胞生成素和特异性。对象的可能依赖项 观察到的对辅助细胞的影响将通过使用CELL进行检查 耗尽和重建实验，并通过使用富集物 骨髓前体细胞密度低。此外，可能的 对血清的依赖也将通过无血清骨来分析 骨髓培养。 2.确定FRP和FRP效应的谱系特异性 抑制素对小鼠外周血祖细胞的影响 造血谱系及其可能的协同作用或 与各种重组因子的拮抗作用。 3.鉴定表达FRP和/或抑制素的细胞类型 进行S1核酸酶分析和RNA原位杂交。这个 生产的FRP/抑制素的功能实体将通过 生物测定和放射免疫测定。 4.探讨观察到的效应的作用机制 通过检测FRP和抑制素对细胞增殖的影响 骨髓红系祖细胞及其与红系祖细胞的结合 K562细胞表面受体的推测。

The overall objective is to investigate the role of two recently purified proteins in human erythropoiesis. Inhibin, a hypophysiotropic hormone which selectively suppresses the secretion of follicle-stimulating hormone (FSH), had been characterized as a heterodimeric protein consisting of alpha- and beta-polypeptides. FSH releasing protein (FRP) was shown to be a dimer consisting of two inhibin beta-chains. It is proposed that they may constitute a new humoral regulatory control for erythropoiesis involving two protein dimers with functionally opposite effects. Based on our recent findings of their effects on erythroid differentiation, the following analyses are proposed to provide insight into their roles in human erythropoiesis. 1. To further characterize the effects of FRP and inhibin on erthroid progenitors: their dose response, dependency upon erythropoietin and specificity. The possible dependency of the observed effects on accessory cells will be examined by using cell depletion and reconstitution experiments, and by using enriched marrow progenitors at low cell density. Furthermore, the possible dependency on serum will also be analyzed byu-sing serum-free bone marrow culture. 2. To determine the lineage specificity for the effects of FRP and inhibin by exploring their effects on progenitor cells of other hematopoietic lineages and also their possible synergistic or antagonistic interactions with various recombinant factors. 3. To identify the types of cells which express FRP and/or inhibin with S1 nuclease analysis and in situ RNA hybridization. The functional entities of FRP/inhibin produced will be examined with bioassay and radioimmunoassay. 4. To investigate the mechanism of action for the observed effects of FRP and inhibin by examining their effects on proliferation of erythroid progenitor cells of bone marrow and their binding with putative surface receptors in K562 cells.